Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Automated scans let scientists track drugs’ broad effects on cells

12.11.2004


’Cytological profiling’ could streamline early phases of drug discovery

Bringing an unprecedented level of automation to microscopy, scientists at Harvard University have developed a powerful new method of visualizing drugs’ multifaceted impact on cells. The technique, which could eventually become a standard tool for drug discovery, is described this week in the journal Science.

Steven J. Altschuler and Lani F. Wu, mathematicians skilled in developing models to find meaningful patterns among mountains of data, worked with Timothy J. Mitchison of Harvard Medical School to automate microscopic imaging of drug-treated cells and recast the resulting scans in a computer-friendly format. The result: a method dubbed "cytological profiling" that trains computers to recognize cell status and health from cellular images, virtually automating microscopic scanning for various types of abnormalities.



"The resulting profiles of cellular changes wrought by drugs at various dosages provide information on drug mechanism that is highly relevant to understanding the specificity and toxicity of drugs," says Altschuler, research fellow at the Bauer Center for Genomics Research in Harvard’s Faculty of Arts and Sciences. "The information gleaned includes many key indicators of drugs’ potential usefulness and limitations as medicines."

"We actually started out on this project thinking that this could be a good research tool," adds Wu, research fellow at the Bauer Center. "We’ve now discovered, to our surprise, that it may also prove a powerful tool for drug discovery."

High-throughput cytological profiling lets scientists test numerous variables at once, wringing countless discrete cellular measurements from a single experiment. Faced with scores of drugs holding the potential to combat a given disease, researchers could hone in on the most promising drugs in a fraction of the time of current methods.

"This technique employs ’guilt by association’ -- if two drugs’ cytological profiles look similar, they probably work through similar mechanisms," Altschuler says. "It’s particularly useful for understanding drug action because it allows us to look at many concentrations of a drug, which is essential for comparing two drugs that may have different potency but act on the same target."

Since they are hardy and flourish even outside the body, the Harvard team used human cancer cells. They placed the cells in 384 minuscule wells in a plastic dish, injected each well with one of 100 drugs -- both medicines and toxins -- at different concentrations, and finished off the plates with11 chemical probes for different proteins and DNA.

After 20 hours of cell growth, the researchers used automated microscopy to collect some half a million images of the treated cells, followed by approximately 5 billion individual measurements of the size, shape, and quantity of different proteins, DNA, and organelles in each. Software developed by Altschuler, Wu, and colleagues allowed them to convert this copious data into profiles of the effects of each drug, yielding distinctive red-and-green "fingerprints" for each, not unlike the color-coded data from a DNA chip.

However, unlike DNA chips that meld bountiful data into an "average" denoted by dots of color on a grid, cytological profiling preserves individual data points -- so researchers can go back and analyze fine-grain information.

"By allowing quantitative measurement of many proteins and structures in cells over many samples, and systematic comparison between samples, our method brings microscopy into the ’-omics’ era, like genomics and proteomics," says Mitchison, of Harvard Medical School’s Institute of Chemistry and Cell Biology and Department of Systems Biology. "This really allows us a much broader view of how cells are affected by a wide range of perturbations."

Cytological profiling may be especially useful, Mitchison says, for evaluating drug candidatesin areas where making a drug with a highly specific biochemical effect is difficult, such as kinase inhibitors. Future applications may include testing the response of cancer cells with different genetic profiles to a spectrum of anti-cancer drugs, which could help predict clinical responses in individual patients.
Alschuler, Wu, and Mitchison were joined in this research, sponsored by the National Cancer Institute and Howard Hughes Medical Institute, by co-authors Zachary E. Perlman and Yan Feng at Harvard Medical School and Michael D. Slack in the Bauer Center for Genomics Research.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>